Clinical Outcomes of Perioperative Desensitization in Heart Transplant Recipients

Abstract

Background. Sensitization remains a barrier to heart transplantation (HT). Perioperative desensitization strategies have been described; however, a paucity of evidence exists to demonstrate efficacy and safety in HT. Methods. This single-center, retrospective study consisted of adults who received an HT. Perioperative desensitization was initiated if virtual crossmatch or flow-cytometry crossmatch was positive. Therapy consisted of plasmapheresis, intravenous immunoglobulin, and rabbit antithymocyte globulin. Historical controls received standard immunosuppression or induction. The primary endpoint was survival at 12 mo. Secondary endpoints included freedom from acute rejection, cardiac allograft vasculopathy (CAV), and infectious complications. Results. Of the 104 patients included, 48 received no induction, 46 received induction, and 10 underwent perioperative desensitization. No differences were observed in the primary endpoint at 12 mo (90.0% versus 97.9%, P = 0.25 for desensitization versus no-induction; 90.0% versus 100%, P = 0.72 for desensitization versus induction). Rates of acute rejection were lower with induction and desensitization compared with no-induction. There were no significant differences in CAV between the groups. Infectious complications were also similar among the groups (10.0% versus 16.7%, P = 0.62 for desensitization versus no-induction; 10.0% versus 30.4%, P = 0.34 for desensitization versus induction). Conclusions. This study suggests that a perioperative desensitization strategy triggered by positive virtual crossmatch or flow-cytometry crossmatch allows for successful transplantation of sensitized HT recipients and results in acceptable rates of survival, rejection, CAV, and infection at 12 mo.

HLA Desensitization in Solid Organ Transplantation: Anti-CD38 to Across the Immunological Barriers

“…Current desensitization strategies have been developed in kidney transplantation and extended to other solid organ transplantation (17)(18)(19)(20)(21). The goal of desensitization regimens in presensitized transplant candidates is twofold including the reduction of anti-HLA level to allow transplantation and the improvement of transplantation outcome through the prevention of ABMR (22).…”

“…Following blood transfusion, pregnancy or previous graft failure, candidates for organ transplantation can become sensitized against HLA and produce circulating anti-HLA antibodies (11,12). In particular, pending on their properties donor-specific anti-HLA antibodies (DSA), are responsible for ABMR leading to allograft dysfunction and graft loss (13)(14)(15)(16)(17)(18). Currently, immunomotoring of the transplant candidate's is routinely performed in order to stratify the immunological risk by determining the presence and specificity of anti-HLA antibodies and potential DSA (11,16).…”

Long-term outcomes of sensitized lung transplant recipients after peri-operative desensitization

“…Of these programs, Courtwright et al recently reported positive short‐term outcomes for their specific protocol for DSA‐positive, complement‐dependent cytotoxicity crossmatch‐negative lung transplants, which includes postoperative PLEX, in addition to IVIG and rituximab if allograft dysfunction is present 12 . Additionally, some heart transplant programs have also reported safe use of similar peri‐operative desensitization regimens for their DSA‐positive transplants 20,21 …”

“…12 Additionally, some heart transplant programs have also reported safe use of similar peri-operative desensitization regimens for their DSA-positive transplants. 20,21 Accepting DSA-positive lung transplants is not yet widespread practice, as evidenced by the significantly lower likelihood of receiving a lung transplant and higher likelihood of dying while on the waitlist among US lung transplant candidates with calculated PRA (cPRA) values exceeding 50%. 10 The peri-operative management of DSA-positive lung transplant recipients is also highly variable among programs, when accepted.…”

Current status and outcomes in heart transplantation: a narrative review

“…Our center's decision implementing desensitization is based on positive virtual or actual cross-matching [110]. Desensitization consists of a 1000-mg methylprednisolone dose and three exchanges of plasma volume performed between induction of anesthesia and allograft reperfusion (Fig.…”